Advances In control of Ischemic Heart Disease

Definition

Impairment of heart function due to decrease in blood flow caused by obstructive changes in coronary circulation to heart (WHC)

Epidemiology

• Modern epidemic worldwide
• Cause of 25 – 30 % deaths in MCST industrilised countries
• Proportional mortality ratio

30 % male

25 % female

• Loss of expectation of life by 3.4 – 9.4 yrs. In male more female
• Despite advances in MGT,

Mortality – 10 % in 1^st yr.

Age standerdised death rates / 1 lac

IHD in India

On screening persons 730 yrs. By 12 left prevalence in Urban – 65.4 / 1000 male

47.8 / 1000 F

In Rural – 22.8 / 1000 M

17.3 / 1000 F

Pattern in India :-

IHD appears 10 yrs. Earlier than in developed.

Ischemic Heart dislast

Clinically, IHD gives rise to

1. Angine Dectoris (A.D.)
2. Myocardial Infacction (M.I.)

Clinical Features

1. Angina Pectoris : 3 forms

1. Chronic Stable (Classic Stable)

Retrosternal Chest pain Episndic, Typically Calsed by exertin and Reletived by rest lasts for 1-5 min.

2. Unnstable (Classic Unstable)

New onset angyny (< 2 months). That is severe &/or frequent (<3 / D). Accelerating angina usually ass with accelerating stenosis in 1 / more eppicard A.

3. Variant (Prinzmetal) A.P.

Chest pain AT rest.

May last for > 10 Min.

Due to focal vaso spasm.

1. Myocardial Ischemia

Retrosternal pain usually radiatim.

Severe / Intolerable. Than A.P.

Lasts longer (>.30 Min).

Not Releived by Rest or N.P.

Nausia, vomittima, Diarrhora.

Excessive Perspiration.

Management of IHD

Main Pharmacotherappeutic Goals

Releif of pain.

Reduction of Myocard Ischemia during attack.

Rediction of silent myocardis.

Improvement in

Pathophyslology

Haemodynamic profile

Neuroendocring activity.

Striated Muscle metabolism

Prevention of Progression

Redution of coronary Atheroma.

Improvement in Risk profile.

Limitation of infarct size

Extension of life span.

Management of A.P.

1. Stable A.P.

Asppirin 75 – 325 mg / d

Intermittent Nitrate Theray

NTG SL TAB 0.3, 0.4, 0.6 mg.

Onset of actopm 1 – 2 min. DurN – 15-40

ISDN SL TAB 2.5 – 5 mg

Onset 2-4 min DURn – 1-2 Hrs.

For Propphylactic use before exertion

NTG T 2.5 and 6.5 mg DASE – 2.5 – 6.5 mg

NTG Skin paste 2% 15 mg / INCH

Dose – 0.25 – 0.5 INCH

T Sorbitrate 5 mg and 10 mg T. Dose – 10-40.

2. MGT of Unstable A.P.

1. Acute Phase (48 – 96 Hrs.)

Aspirin

Heparin

IV Nitrates

B Blockers

Caclium Channel Blockers.

2. Subacute Phase

Oral Nitrates

Heparin

Aspirin

3. Chronic Phase

Aspirin

B Blockers OR

C.C.A.

No smoking, DIET, etc.

MGT of Variant A.P.

IV NTG

C.C.A.

If No Response

Combination Therapy

Amiodaron

Guanethidine

Clonidine

Oral Nitrates for Prophylaaxis

Aspirin

No B Blockers in

Vasospastv Angina

Drug Therapy of A.P. Protocol

Angina

Infrequent Angina

Prophylactic Nitrates for Exert

More Frequent Angina

Angina Frq Limiting Activity

B Blockers

B. B. Contraied

C.C.A.

Angina Still Disabl

Maxlmise Drug Combinations.

Angina Still not Controued

Coronary Angyogr

PTCA CABG

MGI of Myocardial Infarction

1. During 1^st 6 HRS (Hyperacuteph)

Streptokinase

Heparin

Aspirin

2. BETN 6 HRS – 3 Days (Acute Phase)

B Blockers

IV NTG

No.C.C.A.

If B Blockert contraidicated, NON DHP CCA are used.

3. After 3 days (PT is stable)

B Blockers

Oral Nitrates

C.C.A. (Non DHP)

Aspirin.

Advances In Conrol of IHD

1. Pharmacological Advances.
2. Non Pharmacological Advances

Pharmacological Advances

1. Aadvances in Conventional Therapies
2. New Therapies.

1. Advances in Conventional Therapies

1. Nitrates

Preparations Avaliable :

Action :

Prelcad Afterload

Relieve Corcnary spasm

Redistributes Blood along Collateral Channels.

Side Effects :

Headach

Methaemo Globinemia

Hypotension

Syncope

Contrind

Angina by Hypertrophic CMP.

Cardiac Temponade.

Disadv

Tolerance

5. Isosorbide Mononitrate (ISMN) ADV

Completely Bloavallable

Achieves High Blood Conc.

Not converted to Another Active met.

Dose not Undergo Presystemic.

Hepatic Elimination Smaller

Doses Than ISDN Required.

Effect Lasts Longer.

Molsidomine – New Drug

Nitrate like agent that appearc to produce vascular smooth musqe relax by same machanisms as Nitrates.

Undergoing Clinical Trials Recent Studies Show.

NTG Platellet Aggregation INHIB^N

+ VE in folts model

ALSSCC + VE in man in theraputk doses in unstaable angina.

To Avoid Tolerance :

Use Eccentric dosage schedule e.g. BD.

Transdermal patch removed for at Least 8 – 10 Hrs. at night.

Self conrolling Transdermal Patches.

1. Calcium Channel Antagonist

Preparations Available

Action :

Selectively inhibit inward ca 2t current in those Tissues where action Potential has dominant ca 2t dependant upstroke like vascular smooth musue and nodal tissue

Vasodilation

• VE lonotropie Effect

Adverse Effects :

Flushing, Headach, Palpitation

A – V Block, PPT ^N of M.I., Heart Failure.

Contrind :

Sinus Bradycardia, A-V cond Deffects.

Hypotension, Obstr CMP.

Severe Aortic Stenosis.

New Drugs

1. In DHP Nisoldipine, Nitreddipine.
2. In Phenylalkylamines : Gallopamil.
3. In Piperazine : Flunazarine, Panolazine, Tr rmetazodine.

1. & (b) Have same actions as other members in their, class
2. Have some Cytoprctective effects on myocardium

Shown to be Effective as antianginal agents in absence of Haemodynamic Disturbances.

Recent Studies Show :

All C.C.A. Ability of Myocardlum to sustain ischemia

Reversible injury

Delayed by C.C.A.

Reversible injury

They support and protect ischemic fibres during short periods of ischemia

Prevent cumulative damage.

Veradamil Reverses exercise Induced se In coronary resistence, in coronary flob thus improves segmental myocarde. Function verapamil ses Viscocity of Blood Gallopamil prevents sichemia Induced Activation of Neutrophll

Recent studies on C.C.A. and Endothelium show :

CCA also help vasodil ^N through endo thelial mechanism (EDRF) CCA donot affect ca dependent form of No. they interfere e- hypoxia induced damage of endothelium thus no release. They effect of ET₁ induced activ ^N of Mcrophages.

New study in T/t of Aaginagits – Nifedipine :

Gastrointestinal therapeutic system recently developed formul ^N that slowly releases drug in GIT over 24 Hr. Period. When given O.D. same efficacy as S.R. forml ^N of felodipine, verapamil and diltiazem study.

30 – 90 mg of GITS NIF added to existing CCA or B. Blocker therapy.

OBSV ^N Time to onset of angina and extent of st seg. Depression at 24 hr. After 1^st dose

DUR ^N OF Ischemia

Frequency of attacks

NTG of consumption

Advantages :

More effective

Adequate control in stable ang.

Better tolerated in elder.

Can be substituted for conventional T/A

Incidence of adverse R less than con.

Minimum effect on lipid and glucose metabolism.

Reverses L V Hypertrophy

Duration, frequency of attacks.

NTG consumption.

Dosage : start with 30 mg OD

Max 120 mg OD

Disadvantage : Not reported.

Amlodipine :

Current new SHP CCA

Studies show : At 5 – 10 mg /OD )Ther. Dose)

Frequency of attacks

Time of onset.

Consumption of NTG

Total work duration.

Anti anginal efficacy is similar to Diltizem, Nifedipine

B- Blockers + Amlod = Additive effect

Isch. In post infarct.

Advantages :

No adverse effect on rest in HR & BP.

No adverse effect on Cardiac output.

Useful in vasospastic angina.

No adverse effect on lipid and glucose metabolism.

No postural hypotension.

Less tachycardia than nifedipine.

Adverse effect :

Reflex tachycardia.

Antiatherosclerotic effect on CCA.

CCA primarily affect interactions of smooth muscles, endothelial cells, monocytes and platelets which play central role in ATH CCA interact specifically with these cells types and do not allow them to take part in ath. Process.

Recent studies show :

CCA Can lower expression of adhesion molecule in cultured endothelial cell thus redn cell adhesion.

e.g., Nitiendipine lowers surface expression of Adhesion molecule VCAM.

DHP CCA Amlodipine is shown to have antiaggregating effect on platelets mechanism.

Free Ca in platelets.

Release of thromboxane.

CCA can stop process of atherosclerosis and calcification of vessel wall.

Studies :

Animal Study

CCA or prevent deposition of Ca or Cholesterol in vessel wall

Clinical trial :

International Nif. Trial of antiatherotherapy (Intact) :

PTS : Mild / Moderate atherosclerosis tested with nifedipine for 3 years.

Significant effect CN develop of new plaques (P < 0.05)

No resolution of old plaques.

Conclusion from intact :

Ca antagonists may be useful as prophylactic agents in early stages of athesclerosis.

In primary study (1985) (Animal study) CCA retard development of athesclerosis.

CCA & MI

In very acute phase.

Harmful specially in L.V. Dysfunction.

In post infarct period :

Non DHP is useful when used in acute stage of AMI.

Mortality :

Current trend.

No CCA in acute phase of AMI.

After acute stage passed and patient is stable.

Non DHP CCA – Diltiazem, Verapamil used.

Mortality

Sudden death.

Short acting DHP – Nifidipine is harmful in acute phase and postMI

(Because reflex symp. Response TC prediminant vasodilation caused by NIF)

Place of CCA in MI therapy.

Verapamil and Diltiazem : Useful alternative to B blockers when used for secondary prevention in post MI specially with good IV function.

B Blockers

B Blockers available

Action :

By blocking B receptors, HR, BP thus O2 demand.

Adverser : Bradycardia, Hypoglycemia.

Contraindication : LVF, CCF, Bronchial Asthma, Vasospastic angina, Bradycardia.

Studies show that B blockers

1. Inhibit platelet aggregation.
2. Prevent formation of free radicals thus decreasing myocardial ischemia and reperfusion injury.
3. Decreased Renin level : Aldosteron protection from hypokalemia.
4. Block catecholamin activity

4mg stat + 5 mg + 5 mg at 2 min. interval.

Then 50 mg oral every 6 hrs – 2 days

Then 100 mg BD.

Propranolol 1 mg IV every 5 – 10 mins.

Total dose of 0.1 mg/kg then 40 – 60 mg QID.

If there is need of B blocker in contrindicated patients, then Esmolol may help to determine whether patient will tolerate B Blocker.

(D) ACE Inhibitors I IHD

Action :

Less preload and after load thus enhances ventricular emptying and improve myocardial oxygen balance.

Attenuate ventricular remodelling and thus preserve ventricular size and function. Study Ramipril superior to others.

Prevent degradation of Bradykinin & thus effect of Bradykinin effect by 20 – 50 folds.

Ramipril increases number & Prostacyclin release.

Protective effects and improvement of myocardial met.

Trials :

1. Survival Ventricular enlargement

(Save) – 40 % Reduction in remodelling

2. AIRE (Acute infarction Ramipril Efficacy) involve 144 centres over 14 countries

• 27 % reduction in all cases of mortality.
• 19 % reduction in reinfarction, Heart failure & Death stroke.

GISSI – III : Lisinopril study (Wide below)

Indications for ACE I : In IHD :

• AMI with CCF, CAD, HT
• A.P. in elder with L.V. Dysfunction, Pulm EP.
• Specially Imp in PTS with LVF and in large infarcts.

Dose :

Ramipril started in 3 – 10 D

5. mg followed by 5 mg BD.

Lisinopril in Ami :

GISSI – III Trial showed :

Decrease in 6 week mortality from 7.1 % in placebo to 6.3 %.

Decrease in Heart failure and LVF from 17 % to 15.06 ^ (P , 0.05)

Advantages :

Tolerability like other ACEI.

O.D. Dose – More compliance.

Less costly than others.

Does not potentiate hypotension in +NCE of B Blockers.

Dose :

5mg start 5 mg after 24 hours

10 mg after 48 hours.

Then 10 mg OD x 6 weeks.

Place in Therapy

Useful if used early in MI in Haemodynamically stable patients.

Short term therapy is also useful.

Useful in diabetic patients.

4 New ACEI Approved in USA

• Ramipril
• Fosinopril
• Benzazepril
• Quinapril

Newer A II Receptor Antagonists

Peptide Analogues e.g., Losartan.

Advantage : Free of side effects of other ACEI in Developmental Stages

BIB – 839, DUP-532, D-532, SK & F-108566

EXP-3174 (More potent than Losartan)

New studies reveal following actions of ACEI.

Good Anti ISCH Potential improve endothelial function.

Potentiate Nitrate effects.

Prevent Nitrate Tolerance.

May specifically inhibit vascular hypertrophy.

ACEI failed to prevent Restenosis after PTCA.

(E) Combination therapy in IHD Recommended combinations :

Nitrates + B Blockers

Nitrates + CCA

CCA + B Blockers + Nitrates (DHP only)

Advances in antiplatelet drugs

Spirin :

Simple, safest, fastest

Action :

Production of throaboxane A₂ inactivate cyclooxygenase & intewrfere arachidonic acid conversion to PG prevents reinfarction, stroke – Mortal

Dose :

75. 160 – 300 mg / day start immediately

Contrind :

Gastric ulcer, diabetic retinopathy

Side effects :

GIT side effects, renal toxicity (long)

Limitations :

It inhibits only thromboxane A₂ but other agonists for platelents are unaffected so, there is need of drug which will inhibit all the agonists.

In aspirin sensetive PT – ticlopidine

Ticlopidine

• New drug appproved by FDA.
• Anti platelet agent that acts on platelet membrane & changes its reactivity.
• Inhibits aggregation induced by ADP, thromboxane A₂, collagen, thrombin etc.
• Blocks interaction of fibrinogen platelets.
• Action may persist for > 72 Hrs. after discon.

Platelet action comes to normal in 4 – 10 D.

OSE : 250 mg BD.

DV : Wide action

Useful in aspirin sensetive PTS.

Disadv : High cost

Not effective in late reste nosis.

New anticoagulant strategies in IHD heparin :

Prevents formation of large L.V. throm prevents AMI in unstable angina prevents restenosis after thrombolysis.

Convetional dose schedule :

2000 – 5000 U every 6 hrs. SC for 1^st 4 – SD.

Current :

Intial bolus 5000 U IV followed by ifusion of 1000 / Hr. adjusted after 6 hr. aptt with tpa or 6 hrs. after SK.

Limitations :

• Unpredictable dose response
• Narrow benefit : Risk ratio.
• Need for contineuse monitoring
• Limited activity against clot bound thrombin.

L. M. W. H.

More bioavialability at lower doses.

Has adequate anti thrombin effect.

Less disturbances in hemostatic system.

Less risk of bleeding

T½ is more than heparin

Therefore can be given O. D.

No conti. Monitoring required ombination of

Low dose aspirin + low dose warfarin – Trials.

Newer thrombin inhibitors

Hirudine & hirudine peptides in M. I. Imitations of current drugs :

Failure of initial reperfusion.

Inadequate perfusion

Reocclusion

Reinfarction

H or LMWH are ineffective inhibitors of hrombin bound to fibrin or subendo matry

Hirudin : direct thrombin inh. Natural

Hirugen : synthetic blocks interaction of thrombin & fibrinogen weaker.

Hirulog : synthetic blocks active sites of thrombin like hirudin.

Trials :

Montreal heart institute trial

90 Min patency rates : Hirulog 61 % (pco – 02)

Heparin 36 %

Hirudin for improvement of thrombolysis

(HIT) study : Dose of hirudin patency (90 Min) rates.

Limitations :

Lack of dose response curve

Minor bleeds common since no direct

Action on platelets

Rebound phenomenon – Rebound in thrombin formation – rebound hypercoagulation cost very high (> 1000 FOR 3 DAY COURSE).

Place in therapy :

Incidence of recurrent angina out major bleed.

Effective in unstable angina.

Newer direct thrombin inhibitors : (Trials)

Ppack (D – Phenylalanyl 1 – prolyl 1 – argyry – choromethyl keton )

Argatroban

Activated Prot . C.

GP II b / III a antagonists

Why IMP ?

Inding of fibrinogen to activated plaiets is final step in platelet aggrgⁿ & it is mediated by GP II b / III a, so expression of GP is common pathway for plagger of GP is unique to platelets & is most abundant platelet surfac glycoprotein

3. potential therapeutic antagoints

1. Natural – disintegrins
2. Monollonal antibodies to GP receptior
3. Synthetic peptide & nonpeptide ant.

1. Natural – disintegrin several natural peptides from snake venom have high affinity & specificity for all integrins.

Trigramine – For trimersurus 9 ra minpus.

Bitistatine – From bitis artetans

Kistrin – From PIT viper.

ADV : Short T½ therefore reversible therefore chances of bleeding

Sisadv : Not specific for GP but bind all RGD integrin receptor therefore side effects like slockade of adhesive prot to endothelia cells & leucocytes.

GP specific disintegrin –

Barbourin – for rattlesn. S. bari disadv :

Transient thrombody to denia.

Highly antigenic – anaphylaxis

Further study going on.

2. Murin monoclonal antibodies – 763 collar produced mouse monoclonal Ab against GP receptor – ABCI X IMAB or 763 it has

High affinity for GP.

Absclote specificity for GP.

Trials :

7E3 in folts model – Bolus of 7E3 can prevent reocdusion of C. A. following lysis by rtpa mickelson et al showed.

3 hrs. after single dose mg / kg of 7E3

Platelet aggregⁿ by 90 %

Gold et el – In PTS e unstable & ngina & in preventionof restenosis after baloona.

0.05 – 0.2 mg / kg – nce of symptom for > 12 hrs.

No pain for 72 hrs.

35 % in MI, deaths & vnplanned surgery within 30 D of operation.

Fluorescence flow cytometry show :

Effect starts in 30 Min.

7E3 remains of platelets for 14D

Platelet function comes to normal in 48 hr.

Imitations :

Effect is irreversible bleed

Bose is large

Large dose stimulates proleferation of neutralising Ab may restrict 7E3 theraoy or single use (immunogenicity)

Very costly.

Place in therapy – hopeful

3. Synthetic peptide & nonpeptide antagonises e. g. DMP 728, Integrelin

ADV

Same Affinity and specificity as monoclunalal

No side effects like monoclonal Ab.

Limitations :

None is orally bioavailable (Alliv) use limited to acute thrombotic situations.

New orally bioavailable agents

• Sc – 54684 A (Xemlofiban)
• Terafibrian
• MK 383 (Tested in man)

Place in therapy – Hopeful

Advances in thrombolytics

Strategy

Thrombolytic Atents :

1. Streptokinase 9sk0

Adverse Eff :

• Bleeding
• Antigenic – anaphylaxis
• Hypotension

Anisolyted plasminogen streptokinase activator complex (anistreplas (APSAC)

It is monovalent complex betn. Human lysin plasminogen & SK

Dissociation – SK

ADV : Efficacy more than 11 SK.

Infusion finishes in 3 – 4 min. therefore more useful in prehospital MGT

S.E. Same as SK since it contains SK

Single chain urokinase type plasminogen activator (prouroknase, saruplase)

• Single chain glycoprotein
• No specific affinity for fibrin

Vscula :

• Specific affinity for fibrin
• Under clinical evluation

DV over SK

• Less bleeding epecdes
• Trasfusion requirment less
• Superior to SK

S. E. – Bleeding episodes

Two Chain ukoknasl typ plasmin activator (Urokinase)

Activates circulating and fibrin blond

Plasminogen directly

No specific affinity for fibrin

ADV :

• Non antigenci
• Non pyrogenic
• Coagulation deffect mild therefore les bleed
• Can be used in recculsion after SK

Disada : Costier than SK

5)Tissue plasminogen activotor (TPA) (Alteplase)

Synthesised & secreted by encd

High affinity for fibrin

Teplase TPA : Recombinant form

ADV :

• Less antigenic than SK
• Less hypotension than SK.
• Clot dissolution earlier than SK.

(80 min patency – 55 % PTS)

ISADV :

Bleeding more than SK (Cerebral)

Plasninogen activation (reteplase)

• Long T½ therefore twice bolus admn, feasilt
• Rapid and effective C.A. thrombolysis
• Higher patency than alteplase

E

Bleeding

Dose :

IU + 10 U after 30 min.

Gusta III trial is going on.

Table

Comparison of various thrombolytic at 35^th day from ISIS III trial (% of PTS)

Combinations of thrombolytics seful combinations :

• SK (1.5 m u / 1 hr.) + TPA (1 mg / kg)
• TPA + scupa
• UK + Scupa

SK + hirudin – trials goingon

DV :

• High patency rates
• Low reociusion rates
• Less bleeding complications.

ISADV : Very high cost.

New Therapies in 1 HD

Hyperbaric oxygen + thrombolysis in M.I.

Form of inhalation therapy

Ispire pure o₂ > ATM ansolute pressure

Plasma conc. Of dissolved o₂

Normalise o₂ in isch. Tissue

Salvage of isch. Tissue

In animal studies :

HBO + thrombolysis – salvage myocard in ami

In thrials in human being :

Time for pain releif and ST seg. Solution was shorter in HBO GRP.

Mean CPK level at 12 and 24 hrs. reduced in HBO GRP by 35 % (P = 0.03)

Ionale : Con. Of HBO dissolved o₂ in plasma and tissue fluid of breath dedium.

Conclusion :

• HBO + VTPA therapy is feasible and safe.
• Rapid in pain
• Rapid ST seg. Solution
• No obvious adverse sequleae to HBO
• More research is going on.

Potassium channel openers in IHD

New Drugs : Pinacidil, cromakalin nicoradil.

Pinacidil :

Channel opener – K⁺ permeability

Hyperpoleration by opening secfic fraction of ca⁺⁺ dependent K⁺ channels

Ralexⁿ of vascular smooth miscle.

Vasodilation

Pinacidil indirectly initiate closure of voltage dependent Ca⁺⁺ channels - vasodilⁿ

Pinacidil is shown to infarct size.

ADV :

• Controls hypertrophy of L.V.
• Morbidity and mortality
• Improves diastolic function
• Useful in stable and variant angina.

Side Eff. :

• Hypotension
• Intermittent t wave changes.

Nicorandil (BRL 34915)

• Same action as pinacidil
• Additional nitrate like action.
• It is in clinical use in Japan.

Other PCOs

• U 89232
• BMS – 180448 (cardioselective Pco).

Magnesium therapy in M. I.

Tionaly :

PTS MI – Hypomagnesia

Predisposing F for tachyarryth

Tudies :

TEO'S Recent metaanalysis of 7 RCTs.

Deaths in placebo GRP – 8.2 %

Deaths in placebo mg GRP – 3.8 %

55 % reduction in death rate (P < 0.01)

Severe ventr arryth in placebo – 17 %

Severe ventr arryth in mg GRP – 11 %

Leicestar trial

8 mmol MgSO₄ over 5 min then 64 mmol over 24 hrs. Ter 28 D

Mortality in placebo – 10.3 %

Mg GRP – 7.8 %

Therefore relative reduction in death – 24 %

Incidence of LVE by 25 % in mg GRP.

Mechanism :

Arteroolar tone in coronary A

Vasoconstrictive eff. Of catecholamines

Cardiac index

Peripheral resistance

Platelet aggregation

Cardiac arrythmias

Potentiates action of antioxidant V / TE myocardioprotective.

Various Mg ppreparation :

MgSO₄ – 8.12 meg mg / gm salt (2 ml ampoule of 25 %

MgO – 46 meg / gm salt Tab Mg gluconate – 2

MgCL₂ – 9.72 meg / gm salt Tab mg lactate – 85

Commended doses of IV MgSO₄ in ami

22 gm in 1 lt of DW over 48 Hrs.

90 ml / hr x 1^st 3 hrs.

22 ml / hr x next 21 hrs.

11 ml / hr x next 24 hrs.

Arrythmias and coronary spasm – oral mg for 1 yr.

Sale effective, economical

No sofesticated requirments

Hypotension Apnoea

Cardiac Arrest Transient flush

Rind : Shock

Renal failure

Endothlin Antagonists in IHD

Bo 128, PD – 142893, PD – 145065

Bosantan :

• Myocardioprotective
• Immprove cardiac performance
• Vasodilation out reflex tachyca clinic trials.

Antoioxidant therapy in IHD

In IHD – antoxidant status is poor.

Ntioxidants antagonise inactivation of no by emoving superoxide radicals.

Nfusion of VIT. C is being tried.

Captopril, some blocrers and CCA posses antioxident

6. Gene therapy in IHD

Restensosis after baloon angioplasty : Introduction of adenoviral vector encoding midine kinase followed by admisistration fo anciclovir blocked arterial hyperplasia in animal models of restenosis clinical tracs ransferring gene coding vege is effevtive to atherosclerosis in animal m – dels in MICE – autologus bone marr transplantation into Apo – E deficient MICE – brought Sr. Cholestern to normal cevel

May be useful atherosclerosis

7. Newer lipid lowering drugs in IHD

Ecent study – 45 study

Dinavian simvastatin survival study :

IHD plasma chol > statinther > 5 yrs.

In mortality by 12 %

In nonfetal mi by 35 %

Improvement of endothelial function

Plaque stabilisation.

Cent practical recommendations :

If total chol > 212 mg / dl or LDL > 130 mg / dl intake < 30 % fals, < 7 % saturatedafa statin is doc in prevention of IHD.

Lipid lowering drugs

Advantages of statin over old drugs :

• Excessive of LDL therefore in mortality
• Hospital admission rates cost effective
• OD admn – good compliance
• Few side effects.
• Considerable safty.

Newer drugs in IHD

1. Hyperbaric oxygen
2. MgSO₄ M (elurly)
3. Lipid lowering drugs
4. Gene therapy
5. Antioxidant therapy in IHD
6. Endothelian antagonist
7. K channel openers.

Simvastatin :

• DOC in Pts of IHD
• Useful even if PT is diabetic, smoker or HT.
• Independent of therapy e – aspirin or blocken

OSE :

• Simvastatin – 20 – 40 mg / d
• Pravastatin – 20 mg /d

IDE eff. : Gitupset, myopathy

1. Non Pharmacological advances in IHD

• PICS
• CABG
• Baloon angioplasty
• Later gun angioplasty.
• Trans myocardial laser revasculerisation.
• Trans cutaneous spiral cord electrical stimulation.

Conclusion :

Nitrates, blockers CCA milestones in IHD acel getting importance in MI.

New antiplatelet agents, new thromboytics drawing more attraction.

Mg therapy IMP. In MI

PCO₃ very hopeful.

Edothelin ant. Undergoing clinical trials

Hopeful

Gene therapy able to change + NT picture HBO thgerapy feasible, creating interest statin GRP encouraging to IHD PTS.

References :

Recent advances in IHD – No 15

Drugs bulleting – Jan 95 10 (1)

Drugs bulleting – Oct 95 19 (4)

Drugs bulleting – Oct 96 20 (4)